Association of a functional polymorphism in the matrix metalloproteinase-12 promoter region with systemic sclerosis in an Italian population

Mirko Manetti, Lidia Ibba-Manneschi, Cinzia Fatini, Serena Guiducci, Giovanna Cuomo, Claudia Bonino, Laura Bazzichi, Vasiliki Liakouli, Roberto Giacomelli, Rosanna Abbate, Stefano Bombardieri, Carlomaurizio Montecucco, Gabriele Valentini, Marco Matucci-Cerinic

Research output: Contribution to journalArticlepeer-review


Objective. To investigate the possible implication of the matrix metalloproteinase-12 (MMP-12) gene in the genetic predisposition to systemic sclerosis (SSc) susceptibility and clinical phenotype. Methods. The MMP-12 rs2276109 A/G functional polymorphism was selected as a genetic marker and genotyped by polymerase chain reaction-restriction fragment length polymorphism assay in 513 unrelated subjects of Italian white ancestry: 250 patients with SSc [146 limited cutaneous SSc (lcSSc), 104 diffuse cutaneous SSc (dcSSc)] and 263 healthy individuals. Results. A significant difference was observed in MMP-12 rs2276109 genotype distribution between patients with SSc and controls (p = 0.0003), and between lcSSc and dcSSc (p = 0.003). The A allele frequency was significantly higher in patients with SSc than in controls (p = 0.0002), and higher in dcSSc than in lcSSc (p = 0.003). After adjustment for age and sex, the homozygosity for the A allele significantly influenced the predisposition to SSc and to dcSSc (OR 2.44, 95% CI 1.61-3.71, p <0.0001; OR 4.69, 95% CI 2.36-9.33, p <0.0001, respectively). A trend toward an association between the AA genotype and lcSSc was observed (p = 0.06). The homozygosity for the A allele was also significantly and independently associated with antitopoisomerase I antibody positivity (OR 6.39, 95% CI 2.18-18.76, p = 0.001) and interstitial lung disease (OR 2.94, 95% CI 1.25-6.95, p = 0.01). Conclusion. The MMP-12 rs2276109 gene polymorphism may contribute to susceptibility to SSc, and in particular to dcSSc and pulmonary fibrosis. The Journal of Rheumatology

Original languageEnglish
Pages (from-to)1852-1857
Number of pages6
JournalJournal of Rheumatology
Issue number9
Publication statusPublished - Sep 2010


  • Disease susceptibility
  • Gene polymorphism
  • Matrix metalloproteinase-12
  • Scleroderma
  • Systemic sclerosis

ASJC Scopus subject areas

  • Rheumatology
  • Immunology
  • Immunology and Allergy


Dive into the research topics of 'Association of a functional polymorphism in the matrix metalloproteinase-12 promoter region with systemic sclerosis in an Italian population'. Together they form a unique fingerprint.

Cite this